The Human Immunodeficiency Virus (HIV-1) is the etiologic agent of AIDS. The major target for antibodies that can neutralize HIV-1 infection is the exterior envelope glycoprotein, gp120. HIV-1 gp120 is assembled ont he surface of the virus in oligomeric complexes in noncovalent association with the transmembrane glycoprotein, gp41. A major obstacle in HIV-1 vaccine development is the efficient elicitation of broadly-neutralizing antibodies using HIV-1 envelope glycoproteins as immunogens. This difficulty may be, in part, accounted for by the intrinsic poor immunogenicity of gp120. In this study, we propose to test the hypothesis that the immunogenicity of HIV-1 gp120 will be enhanced by covalent linkage to the complement protein, C3d. C3d has been termed a "molecular adjuvant" since it has been shown to enhance the immunogenicity of model proteins in small animals. The use of C3d to overcome the inherent weak immunogenic potential of gp120 is a novel approach that may have significant impact in surmounting a major hurdle in HIV-1 vaccine development.